All publications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
Originally developed for producing large-scale integrated circuits, microfabrication technology has also spurred research and development efforts to manipulate and analyze complex biological fluids at the nano- and microliter scale. The development of miniaturized diagnostic devices for the clinical analysis of blood and other body fluids is an important application of this emerging technology.1-6 For example, point-of-use blood glucose monitoring systems have demonstrated the ability of miniaturized clinical chemistry technology to improve patient care and health care delivery methods.7,8 
Many current diagnostic technologies require sample preparation prior to analysis, and microfluidic devices can be engineered with an integrated isolation process upstream of the analyte detection region. For example, glucose test strips isolate plasma from whole blood with glass fiber filters or microporous membranes.9 Though researchers have reported many lab-on-a-chip diagnostic advances, few results relevant to the microfluidic fractionation of samples are reported.10 For example, Brody et al.11 suggested separating plasma from whole blood using a microfabricated filter device, and reported the filtration of a suspension of microspheres. Wilding et al.12 demonstrated using microfilters to measure white blood cells for genetic analysis, and Duffy et al.13 proposed centrifugation on a rotating “lab disc.” Still, the current state of the art lacks a device capable of isolating for optical visualization a desired number or numerical range of biological particles from a liquid biological sample. Such a device would be of tremendous utility in the point-of-care diagnostics environment by enabling rapid, low-cost diagnoses.
One possible application for microfluidic devices is their use in conjunction with new and reliable biomarkers for diagnosis and treatment of conditions and diseases. For example, recent research has indicated that certain functional declines specific to neurological conditions such as Alzheimer's Disease can be detected in peripheral cells, including platelets. Recent results have also indicated that these same changes can also be detected in platelets from subjects who have been diagnosed with mild cognitive impairment (MCI), often a preclinical precursor to full-blown AD, marked most often by mild memory loss (“monosymptomatic progressive amnesia”).
Microfilters are well suited for microfluidic sample preparation, as they are compatible with current microfabrication technologies, and filtration can be accomplished via pressurization, capillary action, or other induced flows. Further, the precise dimensional and geometric control afforded by micromachining enables the development of optimum filter designs that are not possible with traditional membrane filtration. For example, hollow fiber membranes (commonly used for plasma separation) have bulk flow channel diameters of 200 to 400 μm, while microfluidic channels are readily constructed at dimensions commensurate with blood cells (red blood cells typically measure from 6 to 7 μm in diameter, platelets 1-2 μm). Also, microfilter devices can be fabricated with precise pore dimensions and geometry; in contrast, pore size and geometry in microporous membranes are often heterogeneous. Finally, microfilter devices fabricated with optically transparent material can enable direct visualization of target pathology or labeling of such.